Effect of Xanthohumol on Cognitive Impairment after Myocardial Ischemia-reperfusion in Rats with High-fat Diet
Objective:To investigate the effect of xanthohumol(XN)on cognitive impairment after myocardial ischemia-reperfu-sion in rats with high-fat diet(HFD).Methods:After establishing the rat model of HFD+myocardial ischemia-reperfusion injury(MIRI),rats were divided into Sham group,HFD+MIRI group,HFD+MIRI+L-XN group,HFD+MIRI+M-XN group and HFD+MIRI+H-XN group.Rats in Sham group and HFD+MIRI group were given 0.5％CMC-Na,and rats in HFD+MIRI+L-XN group,HFD+MIRI+M-XN group and HFD+MIRI+H-XN group were given 30,60 and 120 mg/kg/d XN,respectively.The drug was administered continuously for 8 weeks.The Morris water maze test was used to evaluate cognitive function.Serum lipid metabolism and myocardial damage indexes,ox-idative stress and inflammation indexes of myocardial and brain tissues were detected according to the kit instructions,and the myocar-dial and brain tissues were stained by HE and TUNEL.Bax and Bcl2 mRNA were detected by RT-qPCR.BACE1,Aβ1-42,p-NF-κB p65 and Nrf2 proteins were detected by Western blot.Results:Compared with Sham group,the escape latency of HFD+MIRI group in-creased(P＜0.05),the number of times passing through the platform decreased within 60 s decreased(P＜0.05),the levels of TC,TG,LDL-c,FFA,CK-MB,LDH and cTnⅠ all increased(P＜0.05),the level of HDL-c decreased(P＜0.05),the positive rate of TUNEL and the level of MDA,TNF-α,IL-1 β and IL-6 in myocardium and brain increased(P＜0.05),the levels of SOD,GSH-Px and CAT in myocardi-um and brain decreased(P＜0.05),the relative expression of BACE1 and Aβ1-42 protein in brain tissue increased(P＜0.05),the relative expression of Bax and p-NF-κB p65 protein in myocardial and brain tissue increased(P＜0.05),and the relative expression of Bcl2 and nuclear Nrf2 protein decreased(P＜0.05).Compared with HFD+MIRI group,the escape latency of HFD+MIRI+L-XN group,HFD+MIR-I+M-XN group and HFD+MIRI+H-XN group decreased(P＜0.05),the number of times passing through the platform decreased within 60 s increased(P＜0.05),the levels of TC,TG,LDL-c,FFA,CK-MB,LDH and cTnI all decreased(P＜0.05),the level of HDL-c increased(P＜0.05),the positive rate of TUNEL and the level of MDA,TNF-α,IL-1β and IL-6 in myocardium and brain decreased(P＜0.05),the levels of SOD,GSH-Px and CAT in myocardium and brain increased(P＜0.05),the relative expression of BACE1 and Aβ1-42 protein in brain tissue decreased(P＜0.05),the relative expression of Bax and p-NF-κB p65 protein in myocardial and brain tissue decreased(P＜0.05),and the relative expression of Bcl2 and nuclear Nrf2 protein increased(P＜0.05).Conclusion:XN improves cognitive dysfunction in HFD rats after MIRI,and its mechanism involves anti-apoptosis,anti-oxidation anti-inflammation,and inhibition of Aβ formation.
XanthohumolHigh-fat dietMyocardial ischemia-reperfusion injuryCognitive impairmentApoptosisAntioxidationAnti-inflammationAmyloid protein
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